The transferrins, a class of iron-binding proteins widely distributed in physiological fluids and cells, fulfill essential roles in the transport and metabolism of iron. Our goal is to understand the structural foundations and molecular mechanisms underlying their biological functions. In pursuing this, we have chosen to study: (1) the interdependence of the metal and anion binding sites of the transferrins by electron and nuclear magnetic resonance methods; (2) the specific transferrin receptor of erythroid cells, including its molecular properties, subunit structure, interactions with transferrin, and turnover; (3) the iron-donating properties of the two sites of transferrin, to determine whether the structural differences between the sites are mapped into a corresponding difference in function; and (4) the distribution of iron between the binding sites of circulating transferrin. We believe such research should not only elucidate normal events in the regulation of iron metabolism, but may ultimately lead to more rational and effective therapy of derangements in the utilization of this essential metal - among the most common and widespread of human ills.